Physics Athens 2016

PROGRAMME PHYSICS FOR MODERN RADIOTHERAPY Athens, Greece – September 11-15, 2016

Morning Chairs: B. Heijmen, M. Gubanski Afternoon Chairs: A. Henry, T. Depuydt Topic

Sunday 11 September 08.30 – 08.45 08.45 - 09.00 09.00 - 10.00 10.00 - 10.30

Speaker

Welcome address

Introduction to the course

All teachers B. Heijmen

ENTRANCE EXAM

Coffee break

Clinicians: Basics of radiation physics for clinicians ( Niki Room ) Physicists: Modern dose calculation algorithms ( Apollon Hall ) Clinicians : Principles of Radiotherapy Equipment ( Niki Room )

S. Molinelli

10.30 - 11.15

M. Hoogeman

M. Hoogeman

11.15 - 12.00

Physicists : Reference Dosimetry

( Apollon Hall )

B. Heijmen T. Depuydt

12.00 - 12.45 12.45 - 14.00 14.00 - 14.45 14.45 - 15.30 15.30 - 16.00 16.00 - 16.45 Monday 12 September 08.30 - 09.15 09.15 - 10.00 10.00 - 10.30 10.30 - 11.15 11.15 - 12.00 12.00 - 12.45 12.45 - 14.00 16.45- 17.30

IMRT – Physics aspects

Lunch

IMRT - clinical application and impact

M. Gubanski

Volumes in EBRT and introduction to GTV definition

T. Juhler-Nottrup

Coffee break

Imaging for treatment preparation and planning Rotational therapy and flattening filter free dose delivery Morning Chairs: E. Troost, S. Molinelli Afternoon Chairs: T. Juhler-Nottrup, M. Hoogeman Topic

E. Troost

S. Molinelli

Speaker

IGRT - tumour set-up correction strategies IGRT - equipment for in-room imaging

B. Heijmen

A. Henry

Coffee break

Imaging for GTV definition PTV margin calculation

T. Juhler-Nottrup

B. Heijmen

Challenges in dose prescription and plan evaluation

A. Henry

Lunch

Group 1 : Discussions on H&N case - ( Apollon Hall )

A. Henry / M. Hoogeman T. Juhler-Nottrup / T. Depuydt E. Troost / B. Heijmen M. Gubanski / S. Molinelli

Group 2 : Discussions on H&N case - ( Socrates Room )

14.00 - 15.30

Group 3 : Discussions on H&N case - ( Omiros Room ) Group 4 : Discussions on H&N case - ( Solon Room )

15.30 - 16.00 16.00 - 16.45 16.45 – 17.30

Coffee break

Stereotactic radiotherapy

M. Gubanski

Brachytherapy

A. Henry

19.30

Departure Bus for Social Dinner at Palio Tetradio

Afternoon Chairs: A. Henry, T. Depuydt Topic

Tuesday 13 September

Speaker

09.30 - 13.15

FREE MORNING

Physics aspects of proton-, ion-, and electron beam therapy

S. Molinelli

13.15 – 14.00

T. Juhler-Nottrup / T. Depuydt E. Troost / B. Heijmen M. Gubanski / S. Molinelli A. Henry / M. Hoogeman

Group 1 : Discussions on lung case - ( Apollon Hall )

Group 2 : Discussions on lung case - ( Socrates Room ) Group 3 : Discussions on lung case - ( Omiros Room ) Group 4 : Discussions on lung case - ( Solon Room )

14.00 – 15.30

Coffee break

15.30 - 16.00

Clinical aspects and evidence for particle therapy and other novel technology

E. Troost

16.00 - 16.45

16.45 – 17.30

Commissioning and QA/QC of equipment and software

M. Hoogeman

Morning Chairs: E. Troost, B . Heijmen, Afternoon Chairs: M. Gubanski, S. Molinelli Topic

Wednesday 14 September

Speaker

08.30 - 09.15

Radiation Protection

S. Molinelli

09.15- 10.00

In-vivo dosimetry

T. Depuydt

10.00 - 10.30

Coffee break

Group 1 : Discussions on breast case - ( Apollon Hall ) Group 2 : Discussions on breast case - ( Socrates Room ) Group 3 : Discussions on breast case - ( Omiros Room )

E. Troost / B. Heijmen M. Gubanski / S. Molinelli A. Henry / M. Hoogeman T. Juhler-Nottrup / T. Depuydt

10.30 - 12.00

Group 4: Discussions on breast case - ( Niki Room )

Clinicians : Physical principles of advanced Radiotherapy ( Niki Room )

S. Molinelli

12.00 - 12.45

Physicists : Oncologic Concepts ( Apollon Hall )

E. Troost

12.45 - 14.00

Lunch

Clinicians: Dose calculation principles ( Niki Room )

T. Depuydt

14.00 – 14.45

Physicists : QA for advanced delivery techniques ( Apollon Hall ) Clinicians: Calculation of dose in the TPS - ( Niki Room )

M. Hoogeman

T. Depuydt

14.45 – 15.30

Physicists : Non-reference dosimetry ( Apollon Hall )

B. Heijmen

15.30 - 16.00 16.00 - 16.45

Coffee break

Adaptive Radiotherapy

T. Juhler-Nottrup

MEET THE TEACHERS – INFORMAL DISCUSSIONS ON TOPICS BROUGHT UP BY PARTICIPANTS ( Apollon Hall )

16.45 – 17.30

All teachers

Morning Chairs: A. Henry, M. Hoogeman Topic

Thursday 15 September 08.30 - 09.15

Speaker A. Henry

Radiobiology in the clinic

T. Juhler-Nottrup /B. Heijmen

09.15 - 10.00

Field junctions: how, when, and alternatives

10.00 - 10.30 10.30 - 11.15 11.15 - 12.15 12.15- 12.30

Coffee break

Radiotherapy dose and induction of secondary tumors

M. Gubanski B. Heijmen All teachers

EXIT EXAM

Distribution of certificates of attendance

Basics of Radiation Physics for clinicians

Silvia Molinelli Medical Physics Unit, CNAO - Pavia, Italy

Physics for Modern Radiotherapy Athens, Greece – September 11-15, 2016

Contents – Physics behind clinical applications

• Radioactivity • Ionizing radiation and external beam RT • Dose • Interaction with matter

• Energy deposition

Radioactivity

Stability: equilibrium of forces

Line of stability

Too many neutrons for stability b - decay n=>p + +e - + n H-3, C-14, I-131

• H. Becquerel discovered radioactivity in 1896 • A property of nuclei • Due to inherent physical properties, a nucleus may be not stable and likely to undergo a nuclear transformation. Long ranged Electrostatic forces p • This process can be fast (short half life) or slow (long half life). • The time of transformation cannot be predicted for an individual nucleus - it is a random event which can only be adequately described using statistics Short ranged Nuclear forces p n

Too many protons for stability b + decay p + =>n+ e + + n O-16, F-18 electron capture p + + e - =>n+ n Xe-125 → I-125, Tl-201

Activity

Radioactivity it is a random event which can only be adequately described using statistics

• Activity: total number of disintegrations (decays) per unit time - SI unit is the Becquerel (Bq) - nuclear transformation per second – (Curie (Ci) activity of 1 gr of Ra-226)

1 Ci = 37 x 10 9 Bq = 37 GBq

• Activity → A(t) = l N(t) where N(t) is the number of radioactive nuclei at time t

• Decay constant l → characteristic parameter that describes how fast a particular nucleus transforms (probability of disintegration per unit time)

Radioactive Decay

It is only possible to determine the probability of decay in a certain time. In a sample of N nuclei the number of decays per unit time is:

dt dN

l   

N

A =-dN/dt

l eN=N(t) t -

0

2ln

T

2/1

l

Half Life: The time it takes for half the amount of a radioactive material to decay Effective half life (Te) = TpTb/(Tp+Tb) Tp= radioactive decay Tb= biological transport or elimination from the specific site

Annihilation

b +

Radionuclide

 (511 keV)

 (511 keV)

b + + e -

Electron–positron annihilation occurs when an electron (e − ) and a positron (e + ) collide. The result of the collision is the annihilation of the electron and positron, and the creation of gamma ray photons

Radionuclides – Multymodality Imaging

Particle energy (mean)

Radionuclide

Half life

PET

C-11

20.4 min

0.39 MeV

N-13

10 min

0.50 MeV

O-15

2.2 min

0.72 MeV

F-18

110 min

0.25 MeV

Cu-62

9.2 min

1.3 MeV

CT

Ga-68

68.3 min

0.83 MeV

Rb-82

1.25 min

1.5 MeV

In vivo PET dosimetry Range evaluation in Particle Therapy

Proton and Carbon-ion beams induced b + activities

most relevant b + active isotopes of rather long half-lives 15 O (t½ = 2.03 min), 11 C (t½ = 20.38 min), 13 N (t½ = 9.96 min), 38 K (t½ = 7.6 min), 30 P (t½ = 2.5 min) and 34 Cl (t½ = 32.0 min)

sacrum chordoma patient

Frey K. et al. Phys. Med. Biol. 59 (2014)

expected activity

measured activity

Types of Radiation in EBRT

• X rays and gamma rays = photons • electrons and beta particles - negative charge

• neutrons (20000 Pts -> too severe late effects)

• protons - positive charge (≈ 100000 Pts) • Alpha and heavy charged particles (> 10000 Pts with C-ion)

Dose

Gy

Gy (RBE)?

Linear Energy Transfer (LET): Energy transferred per unit of particle path length (keV/ m m)

Damage in nucleus

Ionization tracks

Low LET Sparsely ionizing

Homogeneous deposition of dose

High LET Densely ionizing

Local deposition of high doses

M. Scholz et al. Rad. Res. 2001

Relative Biological Effectiveness (RBE) - particles

RBE-weighted Dose (Gy (RBE)) = Absorbed Dose (Gy) x RBE

D (Co-60; 250kV) D (p-ions)

RBE =

Biological effect (cell inactivation)

RBE is the ratio of the dose of photons, e.g., 60 Co-rays or linear accelerator X- rays, relative to that of protons/ions required to produce a defined biologic response

Radiation through matter – how they interact

• Electromagnetic radiation • Charged particles

• Neutrons

NUCLEAR interactions

ELECTROMAGNETIC interactions in particular inelastic collision with the atomic electrons (Strenght and Range of the Coulomb force) + NUCLEAR interactions

Interactions

Ionization - Excitation Energy transfer to the atom

• Ionization: release of an electron from the atom • Excitation: lift of an electron from an inner shell to one further out

Deexcitation

Energy released by the atom

• Characteristic radiation: the radiation energy is dependent on the electron energy levels (K, L, M etc) and hence characteristic of the given atom • Auger electron

Ionizing Radiation (direct - indirect Effect)

Sufficient energy to ionize atoms (eject an electron or add an additional one)

This leaves a charged ion that will upset chemical bonds

If this affects critical molecules such as DNA it can result in cell damage, mutation or death

Ionizing Radiation (IR)

• Directly ionizing: (charged particles) electrons, protons, light ions … Radiation deposits energy in the medium through direct Coulomb interactions ( → charged) with orbital electrons of atoms in the medium

• Indirectly ionizing: (neutral particles) photons, neutrons

Radiation deposit energy in the medium through a two step process: a charged particle is released in the medium (  -> e - , e + ; n-> p or heavier ions) the released charged particle acts as a directly ionizing radiation

Physics problem in RT

Focus the dose on the target (in space and time)

Dose localization: ability to deliver dose precisely and accurately to a region of interest in the patient → target (improve geometrical dose shaping )

Target definition: - Tumor delineation - Organ Motion - Organ filling - Tumor shrinkage

Imaging – treatment planning - delivery technology

radiation physical properties – technological inventions

The interaction processes of each type of radiation determine → penetration in matter (how much radiation reaches a target) → the amount of dose deposited in the target → Dose conformation around the target (dose to the OARs)

Electromagnetic radiation

NB: l (or n ) does not in itself make the EM wave more or less penetrating! → the key is its interaction with matter , or more specifically, whether the photon energy is right to excite some transition of a charged particle e.g. microwaves penetrate glass very easily, but are strongly absorbed by water; infrared is strongly absorbed by both glass and water, but both transmit visible light …

Photons interaction with matter

Transmission

Absorption • Photoelectric effect • Pair production Interactions are governed by stochastic laws → no prediction of the fate of a single photon → prediction of the fraction of transmitted photons

Scattering • Compton effect • Coherent (Rayleigh)

Photons: photoelectric effect

A photon is absorbed by an atomic electron, which is rejected from the atom The process needs the electron to be bound Kinetic energy of the ejected photoelectron KE is equal to the incident photon energy E 0 minus the binding energy of the orbital electron F : KE = E o - F

KE

E 0

F

Photoelectric effect → split Personality of Light!

Compton Effect

Inelastic scattering of a photon with a quasi-free electron

Decrease in photon energy → Part of the photon energy is transferred to the recoiling electron

Photons – linear attenuation coefficient m = interaction probability per unit path lenght (cm -1 )

d     0 m

N N e

d: absorber thickness m: m (E,Z): linear attenuation coefficient

HVL : half value layer TVL : tenth value layer

Attenuation coefficient m

• each photon interaction process it’s represented by its own attenuation coefficient ( e,t,s,k,z ). The sum of coefficients gives m • Photoelectric absorption, Compton effect and Pair production are dominant in the energy range of interest (0.1 – 100 MeV) Photonuclear interactions (z) m  e + t + s + k + z Photoelectric effect (t)

Pair production (k)

Elastic scattering (e)

Compton effect (s)

Photons Attenuation - Radiography

Radiographic image

• Attenuation is the most important property for medical imaging.

• Differences in the number of photons behind an inhomogeneous absorber create contrast.

m = m ( E,Z ) => same E m lead > m bone > m softT > m air

Photons interaction with matter

Photons interaction with matter

Table illustrating importance of various interactions with energy in H 2 O *

Photon Energy (MeV)

Relative number of interactions (%) t s k

0.01 0.026 0.060 0.150 4.00 10.00 24.00 100.00

95 50 7

5 50 93

0 0 0 0 6

0 0 0 0 0

100 94 77 50 16

23 50 84

* F. Khan, The Physics of Radiotherapy

m: m(E,Z)

Bone

Diagnosis (Z)

Therapy

Soft T

The dominant photon interaction process

RT

CT

Z 4 , E -3

water eq tissues ≈ 7.5

Z eff

Z, E -1/2

Consequences

• Importance of the compton process in the interaction with soft tissue (Z<10) → all imaging modalities will have problems with scattered radiation

Consequences

• MV photons are less suitable for imaging

Check portal film

Reference simulator film

kV CT MV CT

Conversion of m to CT number

m values are scaled to that of water to give the CT number (Hounsfield Unit)

Tissue

CT-number (HU)

Air

-1000

Lung

-300

Fat

-90

m m

- m - m

tissue

water

CT number = 1000 x

Water

0

water

air

White Matter Gray Matter

30 40

TPS: The relative electron density of the irradiated medium can be determined from the CT data set via the conversion between CT numbers and r e

Muscle 50 Trabecular Bone 300-500 Cortical Bone 600 -3000

Photons are indirectly ionizing

Photons deposit energy in the medium through a two step process: 1. energy is transferred to charged particles released in the medium 2. the released charged particles act as directly ionizing radiation

KERMA : K inetic E nergy R eleased per unit Ma ss (J/kg = Gy) Sum of initial kinetic energies transferred from indirectly ionizing radiation to charged particles (electrons) in a sample of matter

• initial kinetic energies of e - 1 contribute to the KERMA as both were generated in V, e - 3 was generated outside V, so does not contribute and e - 2

e -

1

e -

2

• e -

and e -

3 contribute to the Dose in V, while e - 2

1

deposits energy outside V, so does not contribute

V

e -

3

KERMA vs Absorbed Dose

KERMA : K inetic E nergy R eleased per unit Ma ss (J/kg = Gy) Sum of initial kinetic energies transferred from indirectly ionizing radiation (  ) to charged particles (e - ) in a sample of matter

Absorbed Dose : energy absorbed per unit mass (J/kg = Gy) Mean energy transfer imparted by ionizing radiation to matter within volume V

→ E(entering V) – E(leaving V)

absorption of energy does not take place at same location as energy transfer by KERMA → electrons travel in the medium and deposit energy along their tracks, the subsequent imparting of energy to matter ( absorbed Dose ) is spread over distances determined by the ranges of charged particles

Charged Particle Equilibrium

Charged particle equilibrium (CPE) exists if for each charged particle with energy E leaving a volume V , there is an identical particle with same energy E entering V

A B C

• only a fraction of electron track deposits energy in voxel A → dose is low • in voxel B , a new electron starts but there is also part of electron track which started upstream in voxel A → dose is higher B • kinetic energies leaving voxel C is balanced by kinetic energies entering in this volume → equilibrium is reached at C

at C → Dose ≈ KERMA

kV Xrays

Lecture 24 MP 501 Kissick 2012

Depth Dose Profiles - Photons

Build up

Surface dose D s ( skin sparing effect) • photons scattered from collimators, flattening filters, air • backscatter from patient • High E e - produced in air and in any shielding structure close to the pt z < z max • Absorbed dose is much smaller than the transferred energy (KERMA) • Dose buildup results from the relatively long range of secondary charged particles that first are released in the patient by photon interactions and then deposit their kinetic energy

MV Xrays

in the patient

Radiation

D s

Z max

(cm)

E> → < t  > s C • less attenuation • higher penetrating power • more secondary e - • higher electron energy

D max

-> z=z max

≈ range of

100 kVp Xrays 100% 0 Co-60 30% 0.5 6 MV 15% 1.5 18 MV 10% 3.5 secondary particles z > z max Dose decrease for photons attenuation in the patient

e - disequilibrium at tissue interfaces

Soft tissue – lung interface → Less attenuation → Increase in primary beam intensity → Reduction of scattering material → Different electron transport and longer range → lateral loss of e - equilibrium NB: Higher  E → higher e - range → penumbra broadening → wider margins required to compensate for e - disequilibrium (increased dose calculation uncertainty – worst for smaller target volumes)

e - disequilibrium at tissue interfaces

6 MV

18 MV

Pencil beam

Collapsed cone

MC simulations

Knoos T et al. Phys. Med. Biol. 51 (2006 )

Sources and References

• IAEA Radiation protection of Patients http://rpop.iaea.org/RPOP/RPoP/Content/ Radiation Oncology physics handbook http://www-naweb.iaea.org/nahu/dmrp/

• The Physics of Radiation Therapy Faiz M Khan (Lippincott Williams & Wilkins)

• The physical principles of medical imaging http://www.sprawls.org/resources

Sources and References

credits to

Giorgio Baiocco (Physics department, UniPV)

Andrea Mairani (CNAO and HIT)

Modern Dose Calculation Algorithms

Mischa Hoogeman Erasmus MC Rotterdam The Netherlands

Absorbed Dose

 Absorbed dose (also known as total ionizing dose) is a measure of the energy deposited in a medium by ionizing radiation.

 It is equal to the energy deposited per unit mass of medium, and so has the unit J/kg, which is given the special name Gray (Gy).

charged particles

Mechanisms of Interaction

Photo electric effect

Compton scattering

Pair creation

What Happens to the Electrons?

 Electrons move away from the point of creation leaving a trail of ionized atoms.  This is where cell damage is done in a patient  The amount of cell damage is related to the amount of ionizations or energy deposited (absorbed dose!)

Basic Theorems and Principles

 Absorbed dose is the mean energy transfer imparted by ionizing radiation to matter with volume V  Mean energy transfer = E(entering V) – E(leaving V)  KERMA : kinetic energy transferred per unit mass (J/kg = Gy) from photons to charged particles (electrons)  Charged particles (created by primary photons) transfer some of kinetic energy to medium -> absorbed dose and lose some of their energy in the form of radiative losses (bremsstrahlung, etc)  Because electrons travel in the medium and deposit energy along their tracks, absorption of energy does not take place at same location as energy transfer by KERMA (Energy transfer from indirectly ionizing radiation to directly ionizing)

Charged Particle (=Electronic) Equilibrium

 Charged particle equilibrium (CPE) exists if for each charged particle with energy E leaving a volume, there is an identical particle with same energy E entering that volume  Low energy beam enters surface: KERMA is max because fluence is greatest at surface  Low energy beam: KERMA = Dose because the energy is deposited at the interaction point

Low energy

Ignoring brehmstralung

Dose Collision Kerma

Dose (Gy)

depth

Charged Particle (=Electronic) Equilibrium

 High energy beam enters surface: KERMA is max because fluence is greatest at surface  High energy: energy is deposited in front of the interacting photon  lack of energy deposition at the surface  Dose at surface is low (contamination: charged particles generated in linac head)

Transient equilibrium

Transition stage

depth

R

CORRECTION-BASED METHODS

Correction-Based Dose Calculation

Based on dose distributions measured in a water phantom Based on separating the dose into primary and scatter component using empirical methods (e.g. Clarkson scatter integration) scaling the fluence/dose with density (Equivalent Path Length method, Ray Tracing ...) Works well if electron transport and effect of inhomogeneities on scatter component can be ignored  Inhomogeneities were corrected by  

Modeling of Complex Physical Processes

Model Parameters  Finite source size 

Kernel based models (convolution/superposition)

Angular distribution of photons

Primary transmission

Physics models  Monte Carlo 

Extra focal radiation mainly from the primary collimation and the field flattening filter  Differential hardening of the beam by the field  Flattening filter  Curved leave ends  Leaf configuration  Tongue and groove effect  Leaf transmission  Electron contamination  Tissue heterogeneities  …

Grid-based Boltzmann Solvers

Adapted from AAPM presentation External Beam Photon Dose Calculations by T.R. Mackie

KERNEL-BASED METHODS

Kernel-Based Methods

 Combine an analytical calculation of the primary photon interactions with the subsequent transport and energy deposition by secondary particles described by pre-calculated kernels  Point-spread kernel: Absorbed dose from both secondary electrons and photons around the interaction point  Calculated by Monte Carlo in infinite medium of water

Dose Deposition Kernel Low Energy

 Low energy : electron range much shorter than photon mean free path

 Small primary dose region (short BU distance and steep penumbra)

 Wide scatter dose region (high dose outside field)

 Isotropic isolevels (large amount of backscatter)

From: A. Ahnesjö and M.M. Aspradakis, Dose calculations for external photon beams in radiotherapy. Phys Med Biol 44 (1999), pp. R99–R155.

Dose Deposition Kernel High Energy

 High energy : electron track lengths are of the same order as the photon mean free paths

 Large primary dose region (long BU distance & broad penumbra)

 Narrow scatter dose region (low dose outside field)

 Forward directed isolevels (small amount of backscatter)

From: A. Ahnesjö and M.M. Aspradakis, Dose calculations for external photon beams in radiotherapy. Phys Med Biol 44 (1999), pp. R99–R155.

Principle of Convolution (1D)

   xdx xKxT xD ) ( ) (

 )( D = Dose Distribution T = Terma Distribution K = Dose Deposition Kernel 

TERMA

T otal E nergy R eleased in M ass

 The primary photon energy fluence is calculated by ray-tracing primary photon trajectories, including beam modulators, etc.

Kernel-Based Methods

 Energy deposition in homogeneous media can be described through a convolution of the energy released by the primary beam with an energy deposition kernel

Photon fluence

Point spread function (Kernel)

Dose

Pencil Beam Approximation

 Irradiation field decomposed in thin pencil beams

 Superposition of pencil beam kernels in 2D (much faster since 2D integration)

 Summation of individual narrow beams

 Pencil beam kernel cannot be modified locally (i.e. for inhomogeneities)

Kernels are not Invariant in Space

 Energy distribution varies with position in beam  Beam hardening at depth  Off-axis softening

Kernels are tilted

Kernels vary with density

 N 7 operations (including kernel density scaling) to calculate results in N 3 points

Generalization for Primary Beam Spectral Variations

In practice use five energy bins

 Beam hardening accounted for in terma and approximated by precalculated correction factors (Papanikolaou 1993)

Papanikolaou N, Mackie T R, Meger-Wells C, Gehring M and Reckwerdt P 1993 Investigation of the convolution method for polyenergetic spectra Med. Phys. 20 1327–36.

Beam Divergence

 Kernels should ideally be tilted  Approximated by taking inverse square factor at dose deposition site instead of interaction site (Papanikolaou 1993)  Errors above 3% for small SSD, large field size and high energy (Sharpe 1993)

Heterogeneity Correction

All dose fractions of a point kernel are scaled by the mean electron density between the point s of energy release and the point r of energy deposition Approximation for exact kernel for every situation

Range scaling Exact

Fast Point Kernel Convolution (CMS)

Fast Fourier Transform (N 3 log 2 N)  Requires invariant kernel

Separate calculations  Primary kernel  High resolution  Short range  Scatter kernel  Low resolution  Large range

AAA Algorithm of Eclipse (Varian)

 Analytical Anisotropic Algorithm  Three separate sources 1. primary photons 2. extra-focal photons 3. and contaminating electrons 

Effective path length method is used to account for heterogeneities  Lateral scatter: kernels are scaled based on the density

Collapsed Cone

Applies an angular discretization of a parameterized kernel

Collapse cones of equal direction into a common pipe  During each step of the transport along a pipe, kernel energy is picked up and attenuated according to kernel parameters Heterogeneities are accounted for by density scaling 

Dose Calculation time ~MxN 3

Collapsed Cone – Test Geometries

MODEL TYPES A AND B

Two Model Types

Knöös et al.: A. Models primarily based on equivalent path length for inhomogeneity corrections, where electron transport is not separately modeled, and the density changes are sampled along the 1D primary rays. B. Models able to treat in an approximate way the electron transport as well as the secondary photon transport in the medium accounting for density changes, sampled along the full three dimensions.

Clinical Example (Model A vs. Model B)

Katrien De Jaeger, Mischa S Hoogeman, Martijn Engelsman, Yvette Seppenwoolde, Eugène M.F Damen, Ben J Mijnheer, Liesbeth J Boersma, Joos V Lebesque, Incorporating an improved dose-calculation algorithm in conformal radiotherapy of lung cancer: re-evaluation of dose in normal lung tissue, Radiotherapy and Oncology, Volume 69, Issue 1, October 2003, Pages 1-10

Tested Methods

 Anisotropic Analytical Algorithm, version 8.6, Eclipse, Varian (Eclipse AAA)  Collapsed Cone, version 3.1 sp3, Oncentra MasterPlan, Nucletron (OTP CC)  Pencil Beam, version 3.1 sp3, Oncentra MasterPlan, Nucletron (OTP PB)  Collapsed Cone, version 8.0m, Pinnacle, Philips (Pinnacle CC)  Multigrid Superposition, version 4.40, XiO, CMS (XiO Sup)  Fast Fourier Transform Convolution, version 4.40, XiO, CMS (XiO FFT)

T. Nielsen et al. Influence of dose calculation algorithms on the predicted dose distributions and NTCP values for NSCLC patients Med. Phys. 38 (5), May 2011.

Clinical Lung Case (Example)

MONTE CARLO DOSE CALCULATION

Basic Monte Carlo Steps

 Sample energy of photon created by electron

 Sample angles  and  between incoming electron and created photon

 Select distance to the first interaction

 Probability that the photon will travel a distance l without interaction is exp(- m l)

m dl is the probability to interact

 Probability to interact between l and l+dl is given by m exp(- m l) dl

l

 

s

l m

m

lP 

ds e

e  

m

1

0

1

1

l m

) ln(      r

r

e

l

r

1

) 1ln(

m

m

Basic Monte Carlo Steps

 The position of the photon is updated with the travel distance l  The type of interaction will be selected based on the cross section data for the different interactions  The energies and angles of the produced particles will be generated

Basics of Monte Carlo

 Photon Transport

 Small number of interactions  Compton scattering, pair production, …  Electron Transport  Large number of interactions  Elastic scattering

 Inelastic collision causing excitation or ionization  Brehmsstrahlung and emission of X-rays or Auger electrons

Input Particles

 Modelling of radiation source consists of sampling the required information about initial particles (type of particle, starting coordinates, direction cosines, energy, charge and particle weight) The linac can be divided into:  Upper part - components that remain fixed for all possible beams settings (Patient independent)  Lower part - beam modifiers (Patient dependent)   The upper part is modeled only once and a phase-space file is generated at the entrance of the lower part  This file is then used as an input for the MCTP calculation (the lower part and the patient are handled in one process)

Virtual Source Model

 Parameterization of a phase space file

 Several sub-sources serves as a particle generator

Virtual source model from XVMC with two virtual sources, i.e. target and flattening filter

Beam Modifiers

 Most of the calculation time of a MCTP system is spent in the jaws and MLC (when tracking photons and electrons through high-Z materials many particles are lost, so it requires a lots of CPU time to obtain sufficient particles that manage to cross these parts)  To avoid waste of CPU time on photons and electrons tracking through MLC and other collimating devices approximations are introduced  Chen et al (2000): MCDOSE Ray-tracing based method for calculating transmission through MLC geometry (only works with virtual source model)

Beam Modifiers Approximations

A line can be drawn from a sub- source through the MLC to the isocenter plane  In the MLC this line is split up into many short intervals. For each end point of an interval it is determined whether the point falls inside or outside tungsten One simply sums the geometric path lengths X 1 and X 2 in the leaf material to apply an attenuation correction 

X

1

X

2

  yx e , m 

Variance Reduction Techniques

 Particle Splitting  To get more particles to the patient  Split particle close to the patient and simulate track for both particles independently  Statistical weight is adjusted  Often used for the brehmsstrahlung photons in the target inside the linac head  History Repetition  Applied to electrons  …

Danger of not probing all parts of the geometry Reducing calculation time per history means simplifying the physics

Is Monte Carlo Always Perfect?

OCRs for the 35 mm collimator

Measured @ 15 mm Measured @ 100 mm Measured @ 300 mm Calculated @ 15 mm Calculated @ 100 mm Calculated @ 300 mm

1

0.9

0.8

0.7

0.6

0.5

0.4

Normalized Dose

0.3

0.2

0.1

0

0

5

10

15

20

25

30

35

Position (mm)

BOLTZMANN EQUATION SOLVER

Boltzmann Transport Model Assumptions

 The Boltzmann Transport Equation (BTE) is the governing

equation which describes the macroscopic behavior of radiation particles (neutrons, photons, electrons, etc.) as they travel through and interact with matter

 A particle (photon, …) is a point particle moving in straight lines between collisions.  Particles (photons, …) interact with matter through binary collisions and the nuclei are distributed randomly: collision probability per unit distance is constant  The Linear Boltzmann Transport Equation describes the mean behavior of radiation  Linearity:  No particle-particle interactions  isotopic makeup of material constant

Courtesy by Danny Lathouwers

Boltzmann Transport Equation

Courtesy by Danny Lathouwers

Transport and Scatter Equations

Acuros® XB advanced dose calculation for the Eclipse™ treatment planning system. Gregory A. Failla, Todd Wareing, Yves Archambault, and Stephen Thompson

Acuros XB Implementation

 Patient Transport and Dose Calculation 1. Transport of source model fluence into the patient  Repeated for each beam 2. Calculation of scattered photon fluence in the patient 3. Calculation of scattered electron fluence in the patient 4. Dose calculation

Solving Equations by Finite Element Method

 Spatial discretization

 Higher spatial resolution inside beam and reduced resolution in low dose region

 Angular discretization  Energy discretization  Multi-group approach

 Start with highest energy

Courtesy by Danny Lathouwers

From Electron Fluence to Dose

Macroscopic electron energy deposition cross sections in units of MeV/cm

Material density in g/cm 3

Dose to water or dose to medium?

Acuros® XB advanced dose calculation for the Eclipse™ treatment planning system. Gregory A. Failla, Todd Wareing, Yves Archambault, and Stephen Thompson

Stochastic vs. Deterministic Methods

 Stochastic and deterministic methods:  both converge to the same solution  same accuracy

Stochastic (MC) 

Deterministic (AXB) 

Particle tracking process

Provides full solution of photon and electron fluence  Errors come from insufficient refinement of discretized variables  No statistical noise  High efficiency in large attenuation regions and volumes

Errors come from insufficient number of interactions simulated and voxel size

Stochastic errors

 Low efficiency in large attenuation regions and volumes  Parallelization

Adapted from Fogliata Antonella

Courtesy by Danny Lathouwers

Evolution of Calculation Algorithms

Manual – 1D

2D  pencil beam (ECLIPSE – SPB, HELAX (OTP) – TMS, …) 1D heterogeneity correction

2,5 D  ECLIPSE-AAA (pencil beam but with heterogeneity correction ~3D)

3D  convolution/superposition, collapsed cone (CMS, Pinnacle, HELAX (OTP) – CC, Tomotherapy) 3D heterogeneity correction

Monte Carlo and Grid Based Boltzmann Equation solver

Thank you!

References

 A. Ahnesjö and M.M. Aspradakis, Dose calculations for external photon beams in radiotherapy. Phys Med Biol 44 (1999), pp. R99–R155.

 M.R. Arnfield, C.H. Siantar, J. Siebers et al., The impact of electron transport on the accuracy of computed dose. Med Phys 27 (2000), pp. 1266–1274.

 M. Engelsman, E.M. Damen, P.W. Koken et al., Impact of simple tissue inhomogeneity correction algorithms on conformal radiotherapy of lung tumours. Radiother Oncol 60 (2001), pp. 299–309.

F. Kahn, The Physics of Radiation Therapy 4th Edition

 AAPM REPORT NO. 85, TISSUE INHOMOGENEITY CORRECTIONS FOR MEGAVOLTAGE PHOTON BEAMS,Report of Task Group No. 65 of the Radiation Therapy Committee, of the American Association of Physicists in Medicine.  Bielajew AF, Rogers DWO, Nahum AE (1985) Monte Carlo simulation of ion chamber response to 60Co – resolution of anomalies associated with interfaces. Phys Med Biol 30:419–428.

 Monte Carlo Treatment Planning: an Introduction, Report 16 of The Netherlands Commission on Radiation Dosimetry

References

 Keall P J, Siebers J V, Arnfield M, Kim J O and Mohan R 2001 Monte Carlo dose calculations for dynamic IMRT treatments Phys Med Biol 46 929-941

 Mohan R, Antolak J, Hendee W R 2001 Monte Carlo techniques should replace analytical methods for estimating dose distributions in radiotherapy treatment planning Med. Phys. 28 123-126  Papanikolaou N, Mackie T R, Meger-Wells C, Gehring M and Reckwerdt P 1993 Investigation of the convolution method for polyenergetic spectra Med. Phys. 20 1327–36

 NCMG van der Voort van Zyp et al., Radiother Oncol. 2009 Jun;91(3):296-300

 Hol M, MJ, van der Baan P, et al. Accuracy of the Monte Carlo Dose Calculation Algorithm for Cyberknife Treatment of Small Lung Lesions [abstract]. Med Phys 2008;35:2953  T. Knoos, E. Wieslander, L. Cozzi, C. Brink, A. Fogliata, D. Albers, H.Nystrom, and S. Lassen, “Comparison of dose calculation algorithms for treatment planning in external photon beam therapy for clinical situations,” Phys. Med. Biol. 51(22), 5785–5807 (2006).  T. Nielsen et al. Influence of dose calculation algorithms on the predicted dose distributions and NTCP values for NSCLC patients Med. Phys. 38 (5), May 2011  Vassiliev ON, Wareing TA, McGhee J, Failla G, Salehpour MR, Mourtada F. Validation of a new grid-based Boltzmann equation solver for dose calculation in radiotherapy with photon beams. Phys Med Biol. 2010 Feb 7;55(3):581-98.

Prinicples of radiotherapy equipment

Mischa Hoogeman Erasmus MC Rotterdam The Netherlands

Introduction

 Photons (X-rays) cannot be accelerated

 Charged particles, e.g. electrons can be accelerated  What is an electron?

 How to create/free an electron?  How to accelerate an electron?

electron mass = 9.1 × 10 -31 kilograms

X-ray Tube

Coolidge X-ray tube, from around 1917. The heated cathode is on the left, and the anode is right. The X-rays are emitted downwards.

Early devices

Stabilivolt (200 kV)

Betatron

Schematic Accelerator Structure

~ ~ ~ ~

~

-

+ -

+

Traveling Wave Accelerating Guide

-

-

+

+

-

+ +

power in

vacuum

Standing Wave Guide

Electric field at instant t

 End of waveguide terminated by conducting disc   reflected with π/2 phase

 Electrons in 2, 4, 6 will receive no acceleration

Serve only as coupling cavities

Can be moved out to the side of waveguide

Half cycle later: situation has reversed

Traveling vs. Standing Wave Guides

Traveling Wave Guides (Elekta)  Easier, less costly

 Standing Wave Guides (Varian, Accuray)  More efficient

Powering the System: Klystron and Magnetron

10.000 hrs

2.000 hrs

Beam Transport (Chromatic and Achromatic 90 ° Bending)

Linac Head

Photons

Electrons

Energy Distribution Photons vs. Electrons

Photons

Electrons

Papanikolaou (1993)

Beam Collimation

Leaf width 5-10 mm

Rounded leafs

 High leaf velocity required for high dose rate with unflattened beams

Interdigitation

65 mm/s

Wedge

Mechanical fixed wedge

Motorized wedge

Dynamic wedge

Varian and Siemens

CT SCANNER

CT Scanner of Hounsfield

Back Projection

http://www.impactscan.org/impactcourse.htm

Filtered Back Projection

http://www.impactscan.org/impactcourse.htm

Modern CT Scanners for Radiotherapy

 Flat couch top & positioning devices

Wide bore

CT simulation software

External positioning lasers

4D and Respiratory gated CT

64 Multislice

Spiral acquisition

Dual Energy

SPECIAL MACHINES

CyberKnife System Components

kV X-ray source

Robot

6-MV Linac

Synchrony camera

Fixed cones

Robotic table

aSi flat panel imagers

CyberKnife

node

Various node sets

Up to 180 node positions

CyberKnife prostate

4 x 9.5 Gy @ 60%

Tracking tumors that move with respiration

Beam moves with moving tumor

Accuracy better than 3 mm Hoogeman et al. IJROBP 2009

GammaKnife (Elekta)

Invented by Lars Leksell (1967)

 Contains 192 Co-60 sources (half-life is 5.27 years)

Tomotherapy (Accuray)

 Helical delivery of dose by fan beam

Fan beam with binary MLC

MV CT capability

Truebeam STx (Varian)

No flattening filter!

Very high dose rate

Linac Integrated MRI

Raaymakers Phys Med Biol (2009)

MRI-Integrated Radiotherapy Systems

ViewRay

Elekta-Philips Utrecht

Stages of Development Elekta System

Images from Bas Raaymakers

MRIDIAN vs. Elekta System

Clinically released

Under development

Using three Cobalt sources  Linac under development 0.35 Tesla MR scanner  Less magnetic interference, e.g. electron return effect  Hardly any geometric distortion  Less suited for functional imaging

Linear accelerator

1.5 Tesla MRI scanner 

More magnetic interference, e.g. electron electron return effect  Geometric distortion  Functional imaging possible

Vero (Brainlab/Mitsubishi)

Dual orthogonal kV X- ray system Stereoscopic imaging

Fluoroscopy

kV CBCT

Gimbaled LINAC/MLC for real-time tumor tracking

Static conformal beam

Arc therapy

IMRT

Non-coplanar ARC

Proton Therapy Center

Bron: Vu Nguyen / The New York Times

HollandPTC (Erasmus MC, TU Delft, LUMC)

Rotating Gantry

Thank you!

Reference Dosimetry (external beam photon therapy with linacs)

Ben Heijmen

ESTRO - Physics for Modern Radiotherapy Athens 2016

Reference dosimetry

 is about absolute dose measurement (Gy) in reference conditions in water: 10x10 cm 2 , d ref , 100 cm, …

 most important application: calibration of Monitor Unit (MU) chambers in linear accelerators: 1 MU = 1 cGy

Calibration of MU-chamber

MU-chamber  is a transmission ionization chamber  electronics generates ‘counts’ (MUs) after a pre-set charge Q MU measured

Calibration of MU-chamber: electronics is tuned such that 1MU/Q MU corresponds with a dose of 1 cGy in H 2 0 in reference conditions

dose measured with calibrated ionization chamber

What accuracy in delivered dose is required?

Delivered dose is main treatment related predictor for radiotherapy outcome:  local control and toxicity

 MU calibration is one of the principal responsibilities of the medical physicist.  If wrong, dose is too low or too high for all patients.

What accuracy in delivered dose is required?

Prostate cancer

D   

TCP

D

1% change in dose results in  % change in TCP

 =3

5% change in dose results in 15 % change in TCP (50%  35%)

D

1 

? %

D

(Levegrun, IJROBP 2002)

What accuracy in delivered dose is required?

Often,  -values for organs at risk are even higher

A. Brahme Acta Radiologica Oncology 1984

What is needed to perform reference dosimetry in a hospital?

Needed by hospital: 1. calibrated ionization chamber (i.c.): N D,w,Co (dose in H 2 O in 60 Co / charge) 2. protocol to use calibrated i.c. in a therapeutic beam

Choose i.c. recommended by protocol

IAEA-report TRS 398 free download IAEA website

Reference Dosimetry for high energy, external beam photon beam therapy

Outline

1. Global workflow in a hospital 2. Introduction to primary dosimetry standards and standard laboratories (needed for calibration of i.c.) 3. Detailed example of reference dosimetry in the hospital 4. Details and physics of primary standards of absorbed dose to water

Global workflow for reference dosimetry in a hospital 1. Hospital buys i.c. recommended by TRS 398 2. Hospital’s i.c. + electrometer to a standard laboratory for calibration  N D,w,Co : dose in water in 60 Co /reading 3. Absolute water dose measurements in the hospital for MU-chamber calibration, using:

- the calibrated i.c. - TRS398 protocol

Reference Dosimetry for high energy, external beam photon beam therapy

Outline 1. Global workflow the hospital 2. Introduction to primary dosimetry standards and standard laboratories (needed for calibration of i.c.) 3. Detailed example of reference dosimetry in the hospital 4. Details and physics of primary standards of absorbed dose to water

What are dosimetry standards and standard laboratories:

(20 PSDL world wide)

At present only - calorimetry - chemical dosimetry (Fricke) - ionization dosimetry are sufficiently accurate to form the basis of primary standards

Procedure in the standard laboratory for calibration of your ionization chamber

your i.c. in water in reference conditions in 60 Co beam  M Co

their primary or secondary standard in water in 60 Co

 D w,Co

N D,w,Co

= D w,Co

/ M Co

your calibration factor

= dose/reading in 60 Co beam

International Measurement System (IMS) for radiation metrology

BIPM (Bureau International des Poids et Mesures):  set up by the Metre Convention (originally signed in 1875)  serves as the international centre for metrology, laboratory and offices in Sèvres (France)  aim: ensuring worldwide uniformity in matters relating to metrology.

Reference Dosimetry for high energy, external beam photon beam therapy

Outline 1. Global workflow the hospital 2. Introduction to primary dosimetry standards and standard laboratories (needed for calibration of i.c.) 3. Detailed example of reference dosimetry in the hospital 4. Details and physics of primary standards of absorbed dose to water

How to measure absorbed dose in water:

- put ionisation chamber in H 2

O in reference conditions

- irradiate with photon beam  reading M Q

(Q = quality of your beam)

calculate dose to H 2

O in absence chamber:

∙  k i

D w,Q

= M Q

∙N D,w,Co

∙k Q,Co

N

: chamber calibration factor, delivered by standards

D,w,Co laboratory (N D,w,Co

specific for each individual chamber)

k Q,Co

: correction of N D,w,Co

for use in quality Q instead of Co

(depends on chamber type and beam quality Q)

corrections for deviations from reference conditions other than Q, e.g. temperature, air pressure, recombination, etc.  k i : i

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